GENEVA Genes and Environment Initiatives in Type 2 Diabetes (Nurses' Health Study/Health Professionals Follow-up Study)

Type 2 diabetes mellitus (T2D) affects approximately 21 million individuals in the U.S., or almost 10% of the U.S. adult population. Because diabetes is determined by both genetic and environmental factors, a better understanding of the etiology of diabetes requires a careful investigation of gene-environment interactions. The Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS) are well-characterized cohort studies of women and men for whom stored blood and DNA samples are available as well as detailed information on dietary and lifestyle variables. The major goals of the project include: 1. To conduct a GWA analysis among 3,000 cases of T2D and 3,000 healthy controls in NHS/HPFS cohorts. 2. To use information on the joint effects of genes and a list of carefully selected environmental exposures at the initial screening stage to test gene-environment interactions. This approach optimizes our power to detect variants that have a sizeable marginal effect and those with a small marginal effect but a sizeable effect in a stratum defined by an environmental exposure. For this analysis, we have developed a joint test of genetic marginal effect and gene-environment interaction. This flexible two-degree-of-freedom test generally provides greater power than standard methods and has the potential to uncover both marginal genetic effects and stratum-specific effects.

The Version 1 (v1) dbGaP release of data from the GENEVA Diabetes Study (NHS/HPFS) includes data from the NHS only. The Version 2 (v2) dbGaP release includes data from both the NHS and HPFS.

This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to type 2 diabetes mellitus through large-scale genome-wide association studies of well-characterized cohorts of nurses and health professionals. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

• Study Weblinks:
  • Nurses' Health Study
  • Health Professionals Follow-up Study
• Study Design:
  • Case-Control
• Study Type:
  • Nested Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 6033
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

All: part of the Nurses' Health Study or Health Professionals Follow-up Study cohort
Cases: type 2 diabetes mellitus
Controls: no diabetes mellitus

• The Nurses' Health Study (NHS): http://www.channing.harvard.edu/nhs/index.php started in 1976 and the Health Professionals Follow-up Study (HPFS): http://www.hsph.harvard.edu/hpfs/ started in 1986 with information on lifestyle and medical history being collected every 2 years.
• Blood was collected in 1989-1990 for NHS and 1993-1995 for HPFS
• Informed consent for GENEVA was obtained from participants eligible for the nested case-control study in 2007-2008
• Genotyping was completed in December 2008 for NHS and in March 2009 for HPFS.

• Primary Phenotype: Diabetes Mellitus, Type 2

• Principal Investigator
  • Frank B. Hu, MD, PhD. Harvard School of Public Health, Boston, MA, USA; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School.
• Co-Investigators
  • Lu Qi, MD, PhD. Harvard School of Public Health, Boston, MA, USA; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School.
  • Rob M. van Dam, PhD. Harvard School of Public Health, Boston, MA, USA; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School.
  • Peter Kraft, PhD. Harvard School of Public Health, Boston, MA, USA.
  • David J. Hunter, MBBS, ScD. Harvard School of Public Health; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
• Research Fellows
  • Marilyn Cornelis. Harvard School of Public Health, Boston, MA, USA.
  • Qi Sun. Harvard School of Public Health, Boston, MA, USA.
• Institute
  • Harvard School of Public Health, Boston, MA, USA; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School.
• Funding Source
  • U01HG00439. National Human Genome Research Institute, National Instititutes of Health, Bethesda, MD, USA.